Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

EEPD1 is identified as a predictor of prognosis and immune microenvironment through pan-cancer analysis and related to progression of colorectal cancer.

Background: EEPD1 is vital in homologous recombination, while its role in cancer remains unclear. Methods: We performed multiple pan-cancer analyses of EEPD1 with bioinformatics methods, such as gene expression, gene alterations, Prognosis and enrichment analysis, tumor microenvironment, immune cell infiltration, TMB, MSI, immunotherapy, co-expression of genes, and drug resistance. Finally, RT-qPCR, EdU, and transwell assays helped investigate the impact of EEPD1 on CRC cells. Results: EEPD1 was dysregulated and correlated with bad prognosis in several cancers. GSVA and GSEA revealed that EEPD1 was primarily associated with the "WNT_BETA_CATENIN_SIGNALING," "ribonucleoprotein complex biogenesis," "Ribosome," and "rRNA processing." The infiltration of CD8+ T cells, MAIT cells, iTreg cells, NK cells, Tc cells, Tex cells, Tfh cells, and Th1 cells were negatively correlated with EEPD1 expression. Additionally, EEPD1 is significantly associated with TMB and MSI in COAD, while enhanced CRC cell proliferation and migration. Conclusions: EEPD1 was dysregulated in human cancers and correlated with various cancer patient prognoses. The dysregulated EEPD1 expression can affect tumor-infiltrating immune cells and immunotherapy response. Therefore, EEPD1 could act as an oncogene associated with immune cell infiltration in CRC.

Risk factors for anastomotic leak and postoperative morbidity after right hemicolectomy for colon cancer: results from a prospective, multi-centre, snapshot study in China.

BACKGROUND: Right hemicolectomy is the standard treatment for right-sided colon cancer. There is variation in the technical aspects of performing right hemicolectomy as well as in short-term outcomes. It is therefore necessary to explore best clinical practice following right hemicolectomy in expert centres. METHODS: This snapshot study of right hemicolectomy for colon cancer in China was a prospective, multicentre cohort study in which 52 tertiary hospitals participated. Eligible patients with stage I-III right-sided colon cancer who underwent elective right hemicolectomy were consecutively enrolled in all centres over 10 months. The primary endpoint was the incidence of postoperative 30-day anastomotic leak. RESULTS: Of the 1854 patients, 89.9 per cent underwent laparoscopic surgery and 52.3 per cent underwent D3 lymph node dissection. The overall 30-day morbidity and mortality were 11.7 and 0.2 per cent, respectively. The 30-day anastomotic leak rate was 1.4 per cent. In multivariate analysis, ASA grade > II (P < 0.001), intraoperative blood loss > 50 ml (P = 0.044) and D3 lymph node dissection (P = 0.008) were identified as independent risk factors for postoperative morbidity. Extracorporeal side-to-side anastomosis (P = 0.031), intraoperative blood loss > 50 ml (P = 0.004) and neoadjuvant chemotherapy (P = 0.004) were identified as independent risk factors for anastomotic leak. CONCLUSION: In high-volume expert centres in China, laparoscopic resection with D3 lymph node dissection was performed in most patients with right-sided colon cancer, and overall postoperative morbidity and mortality was low. Further studies are needed to explore the optimal technique for right hemicolectomy in order to improve outcomes further.

LncRNA RPLP0P2 Promotes Colorectal Cancer Proliferation and Invasion via the miR-129-5p/Zinc Finger and BTB Domain-Containing 20 Axis.

We previously reported that long non-coding RNA (lncRNA) RPLP0P2 is involved in the progression of colorectal cancer (CRC); however, its molecular mechanisms in CRC remain unclear. In this study, we observed that RPLP0P2 was upregulated in CRC tissues and cell lines. Cell viability was measured using the MTT and colony formation assays. Migration and invasion capabilities were monitored by wound healing, transwell, and immunofluorescence assays. The results showed that RPLP0P2 downregulation inhibited cell viability, migration, and invasion capabilities of CRC cells, accompanied by decreased PCNA, N-cadherin, and Vimentin, and increased E-cadherin expression. Using the DIANA online database, miR-129-5p was identified as a downstream target of RPLP0P2. In fact, RPLP0P2 colocalized with miR-129-5p, acting as a miR-129-5p sponge. MiR-129-5p-inhibition almost abrogated the anti-tumor effects induced by RPLP0P2 inhibition in CRC cells. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential downstream target of miR-129-5p in CRC cells. ZBTB20 overexpression prevented miR-129-5p mimic-mediated anti-tumor effects in CRC cells. A tumor xenograft assay was performed to monitor the role of RPLP0P2 in tumor growth. Of note, in tumor-bearing mice, RPLP0P2-silencing inhibited tumor growth, followed by increased miR-129-5p and decreased ZBTB20 expression. Our results suggest that lncRNA RPLP0P2 functions as an oncogene that promotes CRC cell proliferation and invasion via regulating the miR-129-5p/ZBTB20 axis, thus, it may serve as a candidate target for CRC interventional therapies.

Herbal medicine and its impact on the gut microbiota in colorectal cancer.

It is well-established that there are trillions of gut microbiota (GM) in the human gut. GM and its metabolites can reportedly cause cancer by causing abnormal immune responses. With the development of sequencing technology and the application of germ-free models in recent years, significant inroads have been achieved in research on GM and microbiota-related metabolites. Accordingly, the role and mechanism of GM in colorectal cancer (CRC) development have been gradually revealed. Traditional Chinese medicine (TCM) represents an important source of natural medicines and herbal products, with huge potential as anti-CRC agents. The potential application of TCM to target gut microbes for the treatment of colorectal cancer represents an exciting area of investigation.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Loss of exosomal miR-200b-3p from hypoxia cancer-associated fibroblasts promotes tumorigenesis and reduces sensitivity to 5-Flourouracil in colorectal cancer via upregulation of ZEB1 and E2F3.

Hypoxia-mediated tumor progression is a major clinical challenge in human cancers including colorectal cancer (CRC). In addition, exosome-mediated transfer of miRNAs from cancer-associated fibroblasts (CAFs) to cancer cells could promote tumor progression. However, the mechanisms by which hypoxia CAFs promotes CRC progression remain largely unknown. CAFs and normal fibroblasts (NFs) were isolated from CRC tissues and adjacent normal tissues. Next, exosomes were isolated from the supernatant of CAFs that cultured under normoxia (CAFs-N-Exo) and hypoxia (CAFs-H-Exo). RNA-sequencing was then performed to identify differentially expressed miRNAs (DEMs) between CAFs-N-Exo and CAFs-H-Exo. Compared with exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs were able to promote CRC cell proliferation, migration, invasion, stemness and reduce the sensitivity of CRC cells to 5-fluorouracil (5-FU). In addition, miR-200b-3p levels were dramatically decreased in exosomes derived from hypoxic CAFs. Remarkably, increasing exosomal miR-200b-3p in hypoxic CAFs reversed the promoting effects of hypoxic CAFs on CRC cell growth in vitro and in vivo. Furthermore, miR-200b-3p agomir could inhibit CRC cell migration, invasion, stemness and increase the sensitivity of SW480 cells to 5-FU via downregulating ZEB1 and E2F3. Collectively, loss of exosomal miR-200b-3p in hypoxia CAFs could contribute to CRC progression via upregulation of ZEB1 and E2F3. Thus, increasing exosomal miR-200b-3p might serve as an alternative approach for the treatment of CRC.

The CT-based intratumoral and peritumoral machine learning radiomics analysis in predicting lymph node metastasis in rectal carcinoma.

BACKGROUND: To construct clinical and machine learning nomogram for predicting the lymph node metastasis (LNM) status of rectal carcinoma (RC) based on radiomics and clinical characteristics. METHODS: 788 RC patients were enrolled from January 2015 to January 2021, including 303 RCs with LNM and 485 RCs without LNM. The radiomics features were calculated and selected with the methods of variance, correlation analysis, and gradient boosting decision tree. After feature selection, the machine learning algorithms of Bayes, k-nearest neighbor (KNN), logistic regression (LR), support vector machine (SVM), and decision tree (DT) were used to construct prediction models. The clinical characteristics combined with intratumoral and peritumoral radiomics was taken to develop a radiomics and machine learning nomogram. The relative standard deviation (RSD) was used to predict the stability of machine learning algorithms. The area under curves (AUCs) with 95% confidence interval (CI) were calculated to evaluate the predictive efficacy of all models. RESULTS: To intratumoral radiomics analysis, the RSD of Bayes was minimal compared with other four machine learning algorithms. The AUCs of arterial-phase based intratumoral Bayes model (0.626 and 0.627) were higher than these of unenhanced-phase and venous-phase ones in both the training and validation group.The AUCs of intratumoral and peritumoral Bayes model were 0.656 in the training group and were 0.638 in the validation group, and the relevant Bayes-score was quantified. The clinical-Bayes nomogram containing significant clinical variables of diameter, PNI, EMVI, CEA, and CA19-9, and Bayes-score was constructed. The AUC (95%CI), specificity, and sensitivity of this nomogram was 0.828 (95%CI, 0.800-0.854), 74.85%, and 77.23%. CONCLUSION: Intratumoral and peritumoral radiomics can help predict the LNM status of RCs. The machine learning algorithm of Bayes in arterial-phase conducted better in consideration of terms of RSD and AUC. The clinical-Bayes nomogram achieved a better performance in predicting the LNM status of RCs.

Loss of exosomal micro-RNA-200b-3p from hypoxia cancer-associated fibroblasts reduces sensitivity to 5-flourouracil in colorectal cancer through targeting high-mobility group box 3.

Hypoxia-mediated tumor progression is a major problem in colorectal cancer (CRC). MicroRNA (miR)-200b-3p can attenuate tumorigenesis in CRC, while exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) can promote cancer progression. Nevertheless, the function of exosomal miR-200b-3p derived from CAFs in CRC remains unclear. In this study, CAFs and normal fibroblasts (NFs) were isolated from CRC and adjacent normal tissues. Next, exosomes were isolated from the supernatants of CAFs cultured under normoxia and hypoxia. Cell viability was tested using the cell counting kit-8 assay, and flow cytometry was used to assess cell apoptosis. Cell invasion and migration were evaluated using the transwell assay. Dual-luciferase was used to investigate the relationship between miR-200b-3p and high-mobility group box 3 (HMBG3). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the miR-200b-3p and HMBG3 level. Our results found that the miR-200b-3p level was sharply reduced in CRC tissues compared to adjacent normal tissues. Additionally, the miR-200b-3p level was reduced in exosomes derived from hypoxic CAFs compared to exosomes derived from CAFs under normoxia. Exosomes derived from hypoxic CAFs weakened the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. However, hypoxic CAFs-derived exosomes with upregulated miR-200b-3p increased the sensitivity of CRC cells to 5-fluorouracil (5-FU) compared to hypoxic CAFs-derived exosomes. In addition, HMBG3 was identified as the downstream target of miR-200b-3p in CRC cells, and its overexpression partially reversed the anti-tumor effect of the miR-200b-3p agomir on CRC via the mediation of the ß-catenin/c-Myc axis. Furthermore, compared to exosomes derived from normoxia CAFs, exosomes derived from hypoxic CAFs weakened the therapeutic effects of 5-FU on CRC in vivo via the upregulation of HMGB3 levels. Collectively, the loss of exosomal miR-200b-3p in hypoxia CAFs reduced the sensitivity to 5-FU in CRC by targeting HMGB3. Thus, our research outlines a novel method for the treatment of CRC.

A Tumoral and Peritumoral CT-Based Radiomics and Machine Learning Approach to Predict the Microsatellite Instability of Rectal Carcinoma.

Objective: To predict the status of microsatellite instability (MSI) of rectal carcinoma (RC) using different machine learning algorithms based on tumoral and peritumoral radiomics combined with clinicopathological characteristics. Methods: There were 497 RC patients enrolled in this retrospective study. The tumoral and peritumoral CT-based radiomic features were calculated after tumor segmentation. The radiomic features from two radiologists were compared by way of inter-observer correlation coefficient (ICC). After methods of variance, correlation, and dimension reduction, six machine learning algorithms of logistic regression (LR), Bayes, support vector machine, random forest, k-nearest neighbor, and decision tree were conducted to develop models for predicting MSI status of RC. The relative standard deviation (RSD) was quantified. The radiomics and significant clinicopathological variables constituted the radiomics-clinicopathological nomogram. The receiver operator curve (ROC) was made by DeLong test, and the area under curve (AUC) with 95% confidence interval (95% CI) was calculated to evaluate the performance of the model. Results: The venous phase of CT examination was selected for further analysis because the proportion of radiomic features with ICC greater than 0.75 was higher. The tumoral and peritumoral model by LR algorithm (M-LR) with minimal RSD showed good performance in predicting MSI status of RC with the AUCs of 0.817 and 0.726 in the training and validation set. The radiomic-clinicopathological nomogram performed better in both the training and validation set with AUCs of 0.843 and 0.737. Conclusion: The radiomics-clinicopathological nomogram demonstrated better predictive performance in evaluating the MSI status of RC.

HMGB3 is a Potential Therapeutic Target by Affecting the Migration and Proliferation of Colorectal Cancer.

Colorectal cancer is one of the common malignant tumors in the digestive system, with high incidence and mortality rate. Therefore, there is an urgent need to identify and develop new molecular targets for colorectal cancer treatment. Previous studies have pointed out the important role of HMGB3 in tumors, and how it works in colorectal cancer needs to be studied in depth. In this study, we found that HMGB3 was highly expressed in COAD in the cBioPortal and GEPIA2 databases. Kaplan-Meier analysis showed that compared with patients with lower HMGB3 levels, patients with higher HMGB3 levels had poorer OS (p = 0.001). We also found a correlation between HMGB3 expression and immune infiltration of CRC. To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and ß-catenin proteins after knockdown of HMGB3. Taken together, HMGB3 can be an effective target for CRC treatment in the future, and we have reason to believe that HMGB3 will be of greater value in more tumors in the near future.

BHLHE41 Overexpression Alleviates the Malignant Behavior of Colon Cancer Cells Induced by Hypoxia via Modulating HIF-1α/EMT Pathway.

Objective: BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods: The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results: Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions: BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.

WITHDRAWN: LncRNA USP1 Knockdown Weakens the Progression of Colorectal Cancer via Modulating UBAP2L-Smad7-TGF-ß Pathway

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Regulatory functions of miR­200b­3p in tumor development (Review).

MicroRNAs (miRNAs/miRs), non­coding single­stranded RNAs of length 18­24 nucleotides, can modulate gene expression through post­transcriptional control. As such, they can influence tumor proliferation, apoptosis, invasion, metastasis as well as chemotherapy resistance by regulating certain downstream genes. In this context, miR­200b­3p, one particular member of the miR­200 family, possesses the ability to suppress tumor progression. However, many studies have suggested that, in certain cases, this miRNA may also promote the development of some tumors due to differences in the microenvironments and molecular backgrounds of different cancers. This review summarizes previous studies on the involvement of miR­200b­3p in tumors, including the underlying mechanism.

Comparison of laparoscopic and open colectomy for splenic flexure colon cancer: a systematic review and meta-analysis.

PURPOSE: This study examined the short- and long-term outcomes of laparoscopic and open splenic flexure colon cancer (SFCC) surgery. METHOD: Systematic literature searches were performed in PubMed and Ovid to compare laparoscopic and open colectomy for SFCC. The last search was conducted on November 7, 2021. Surgical and survival outcomes were collected and analyzed. This meta-analysis was performed using Review Manager Software (v 5.3). RESULTS: This study included seven publications with 2397 patients published between 2011 and 2021. A significant difference in operative time was seen in the laparoscopic group (P = 0.01, WMD = 50.13, 95%CI [10.32, 89.94], I2 = 97%); loss of blood estimated (P < 0.001, WMD = -101.88, 95%CI [-161.65, -42.11], I2 = 82%) and the incidence of overall complications (P < 0.001, OR = 0.53, 95%CI [0.38, 0.75], I2 = 0%) of laparoscopic procedure were greatly decreased. There were similar results as compared in the two groups in terms of lymph node harvesting (P = 0.71, WMD = 0.49, 95%CI [-2.13, 3.12], I2 = 93%) and the distance of proximal (P = 0.50, WMD = -1.09, 95%CI [-4.26, 2.08], I2 = 96%) or distal (P = 0.18, WMD = 2.44, 95%CI [-1.13, 6.01], I2 = 97%) resection margin. In addition, no significant differences were observed on overall/disease-free survival over 3/5 years between the two procedures. An analysis of subgroups that used propensity matching scores produced similar results. CONCLUSION: The laparoscopic procedure is clinically safe and feasible for SFCC. It shows the advantages in decreasing intraoperative blood loss and overall complications, and the long-term survival outcomes would not be affected. Randomized clinical trials with a larger sample size are warranted in the future for further investigation.

Downregulation of lncRNA RPLP0P2 inhibits cell proliferation, invasion and migration, and promotes apoptosis in colorectal cancer.

Recent studies have revealed that long noncoding RNAs (lncRNAs) are closely associated with colorectal cancer (CRC); however, the role of the lncRNA RPLP0P2 in CRC remains largely unknown. In the present study, RNA expression profiles of CRC were collected from The Cancer Genome Atlas database and the prognosis of CRC with respect to RPLP0P2 was assessed. Subsequently, RPLP0P2 expression was knocked down in the human CRC cell line RKO using a short hairpin RNA (shRNA) lentivirus, and the biological behaviors of the cells, such as proliferation, migration, cell cycle progression and apoptosis, were examined. The results demonstrated that the expression levels of RPLP0P2 were higher in CRC tissue compared with those in normal tissue, and RPLP0P2 was associated with prognosis. RPLP0P2 knockdown significantly decreased cell colony formation, migration and invasion, and arrested CRC cells in the S phase to G2/M phase transition. Furthermore, apoptosis was significantly increased in CRC cells infected with the RPLP0P2 shRNA lentivirus compared with in the control group. In conclusion, RPLP0P2 may promote proliferation, invasion and migration, and inhibit apoptosis of CRC cells, suggesting that RPLP0P2 may function as an oncogene in CRC.

Polypectomy During Both Insertion and Withdrawal Phase Versus During Withdrawal Phase Only: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: This study aimed to compare polypectomy during both insertion and withdrawal phase versus during withdrawal phase only. Method: We performed literature searching in PubMed and Ovid for randomized clinical trials (RCTs) that compared polypectomy during both insertion and withdrawal phase versus during withdrawal phase only on April 3, 2020. The primary outcome was adenoma detection rate (ADR). Results: Five RCTs published between 2012 and 2020 with a total of 2694 individuals were included in this meta-analysis. No significant difference was observed between the two groups for ADR (P = .99, odds ratio = 1.00, 95% confidence interval [CI] 0.84-1.19, I2 = 0%), or average number of adenomas per individuals (P = .53, weighted mean difference [WMD] = 0.04, 95% CI -0.09 to 0.17, I2 = 30%). Besides, polypectomy during both insertion and withdrawal group showed significantly longer time for insertion phase (P = .01, WMD = 2.16, 95% CI 0.47-3.84, I2 = 95%), and shorter time for withdrawal phase (P = .010, WMD = -2.32, 95% CI -4.09 to -0.56, I2 = 94%), although the total procedure time was not significantly different between the two groups. Conclusion: No obvious advantages were observed for polypectomy during both insertion and withdrawal phase. We are looking forward to the long-term outcomes of these studies. More studies are warranted in the future for further exploration, especially the detection rate of small lesions.

Laparoscopic Complete Mesocolic Excision Versus Noncomplete Mesocolic Excision: A Systematic Review and Meta-analysis.

BACKGROUND: Complete mesocolic excision (CME) emphasizes sharp dissection along the mesocolon plane and ligation of the supplying vessels at their origin. Although laparoscopic CME is reported to be feasible and safe, the benefit of laparoscopic CME over noncomplete mesocolic excision (NCME) remains unclear. This meta-analysis aimed to compare the safety, quality, and effect of laparoscopic CME with NCME. MATERIALS AND METHODS: A systematic literature search with no limits was performed in PubMed, Embase, and Web of Science on March 27, 2020. Studies comparing laparoscopic CME with NCME were enrolled. Outcomes of interests included intraoperative, pathologic, postoperative, and survival outcomes. RESULTS: Seven studies (5 articles and 2 conference abstracts) published between 2015 and 2020 with a total of 1595 patients (742 by CME and 853 by NCME) were enrolled. Compared with NCME, laparoscopic CME was associated with less intraoperative blood loss [P<0.001, weighted mean difference (WMD)=-12.01, 95% confidence interval (CI): -13.56 to -10.45, I2=44%], more harvested lymph nodes (P<0.001, WMD=6.50, 95% CI: 3.57-9.42, I2=89%), longer length of specimens (P=0.004, WMD=3.57, 95% CI: 1.12-6.03, I2=93%), longer distance from tumor to high tie (P<0.001, WMD=1.36, 95% CI: 0.87-1.85, I2=76%), and longer distance from nearest bowel wall to high tie (P<0.001, WMD=1.36, 95% CI: 0.87-1.85, I2=85%). No differences were observed in terms of operative time, postoperative complications, wound infection, ileus, proximal, and distal resection margin or disease-free survival between 2 groups. CONCLUSIONS: The currently limited evidences suggest that laparoscopic CME can slightly decrease intraoperative blood loss and improve specimen quality, but its safety and survival benefits need to be further studied. High-quality evidences are needed before laparoscopic CME can be recommended as the standard procedure for colon cancer surgery.

Schizandrin A exhibits potent anticancer activity in colorectal cancer cells by inhibiting heat shock factor 1.

Heat shock factor 1 (HSF1) is a powerful multifaceted oncogenic modifier that plays a role in maintaining the protein balance of cancer cells under various stresses. In recent studies, there have been reports of increased expression of HSF1 in colorectal cancer (CRC) cells, and the depletion of the HSF1 gene knockdown has inhibited colon cancer growth both in vivo and in vitro. Therefore, HSF1 is a promising target for colon cancer treatment and chemoprevention. In the present study, we found that Schizandrin A (Sch A) significantly inhibited the growth of CRC cell lines by inducing cell cycle arrest, apoptosis and death. Through HSE luciferase reporter assay and quantitative PCR (qPCR), we identified Sch A as a novel HSF1 inhibitor. In addition, Sch A could effectively inhibit the induction of HSF1 target proteins such as heat-shock protein (HSP) 70 (HSP70) and HSP27, whether in heat shock or normal temperature culture. In the Surface Plasmon Resonance (SPR) experiment, Sch A showed moderate affinity with HSF1, further confirming that Sch A might be a direct HSF1 inhibitor. The molecular docking and molecular dynamic simulation results of HSF1/Sch A suggested that Sch A formed key hydrogen bond and hydrophobic interactions with HSF1, which may contribute to its potent HSF1 inhibition. These findings provide clues for the design of novel HSF1 inhibitors and drug candidates for colon cancer treatment.

MEIS2 promotes cell migration and invasion in colorectal cancer.

Colorectal cancer (CRC) is one of the most common types of malignancy worldwide. Distant metastasis is a key cause of CRC­associated mortality. MEIS2 has been identified to be dysregulated in several types of human cancer. However, the mechanisms underlying the regulatory role of MEIS2 in CRC metastasis remain largely unknown. For the first time, the present study demonstrated that MEIS2 serves a role as a promoter of metastasis in CRC. In vivo and in vitro experiments revealed that knockdown of MEIS2 significantly suppressed CRC migration, invasion and the epithelial­mesenchymal transition. Furthermore, microarray and bioinformatics analyses were performed to investigate the underlying mechanisms of MEIS2 in the regulation of CRC metastasis. Additionally, it was identified that a high expression of MEIS2 was significantly associated with a shorter overall survival time for patients with CRC. The present study demonstrated that MEIS2 may serve as a novel biomarker for CRC.